IU School of Medicine Targets Ovarian Cancer with Department of Defense Grant

INDIANAPOLIS -- The U.S. Department of Defense has awarded a three-year, $2 million grant to Indiana University School of Medicine for research to improve the effectiveness of treatments for ovarian cancer.

Nearly one woman in 70 will develop ovarian cancer in her lifetime. Called the "silent killer," ovarian cancer is not diagnosed in the majority of women until it has spread to other parts of the body, making it more difficult to treat. Cancer confined to the ovary frequently can be cured with surgery and possibly additional chemotherapy or radiation treatments. Initially, the tumors respond well to chemotherapy or radiation, however, the tumors can become resistant to treatment.

Making the tumor cells more sensitive to chemotherapy or radiation, while protecting normal cells in the body, is the focus of the DoD-funded program at the IU School of Medicine.

"We have a unique opportunity with this grant to capitalize on our strengths in ovarian cancer research and therapy to find new therapeutic strategies for treating this disease," said Stephen D. Williams, M. D., director of the Indiana University Cancer Center and principal investigator for the grant. "The research we will be doing represents the next step in the development of beneficial treatments for ovarian cancer."

The overall goal of the project is to increase the cure rate for ovarian cancer. Strategies to do this include identifying methods of altering genes that either by themselves or in combination would increase sensitivity of human ovarian cancer cells to therapy, and to develop methods of delivering the gene therapy treatment to cancer cells only, leaving normal cells free from damage from chemotherapy or radiation. Initial research will be conducted in cell lines in the laboratory and then evaluated in mice.

The laboratory projects focusing on these strategies involve finding a way to "confuse" or inhibit one of the body's mechanisms to repair the cell damage caused by chemotherapy or radiation. This would allow researchers to create ovarian tumor cells that are more responsive to chemotherapy and radiation, thus allowing lower, less toxic doses of the drugs or radiation to be used. The lower doses should provide less toxicity to normal cells. These research projects are being conducted by Mark R. Kelley, Ph.D., the Jonathan and Jennifer Simmons Professor of Pediatrics, and Suk-Hee Lee, Ph.D., associate professor of biochemistry and molecular biology.

In a third project supported by the grant, Jean A. Hurteau, M.D., associate professor of obstetrics and gynecology, will look at cell division within the ovarian cancer cell to determine if specific proteins can be used to disrupt the cycle and cause the cancer cells to die.

Kenneth P. Nephew, Ph.D., assistant professor in the Medical Sciences Program in Bloomington, is looking at genes that serve as "on-off" switches specific to ovarian cancer cells. These "switches" are part of the natural cell division process. Although several switches, also known as cell promoters, are known, none has been isolated that only targets ovarian tumors and not other critical tissues, such as the brain, liver or blood cells. This discovery is instrumental to the development of gene therapy for ovarian cancer.

Another component of the study is to evaluate the feasibility of the laboratory research in mice. Robert M. Bigsby, Ph.D., associate professor of obstetrics and gynecology, is the principal investigator of this portion of the research. Dr. Bigsby will collaborate with the other study investigators to further evaluate in animals the possibility of sensitizing ovarian cancer cells to therapy to increase the effectiveness of treatments.

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Media Contact: Mary Hardin
Tel: (317)274-7722
Email: mhardin@iupui.edu

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